Pulmonary tissue produces high amounts of prostaglandins (PG), leukotrienes (LT), and hydroxy fatty acids (HFA) in response to a number of stimuli or pathological states. These lipids have diverse biological activities. The goal of this study is two-fold: first to develop an understanding of factors that control the biosynthesis of these lipids and second to determine their role in the secretory and inflammatory processes of the lung. We have chosen to study the biosynthesis of these lipids in dog tracheal epithelial cells and to determine their role in control of C1- and mucus secretion. Dog trachea cells make primarily PGD2 and a number of LTs. LTC4, LTB4 and two unknown LTs are also produced. While C1- secretion appears to be primarily under control of PGD2 formation, other data suggest a regulatory role for the LTs. We intend to characterize further the LTs formed and relate them to C1- secretion. We are also examining the formation of LTs in response to asbestos exposure. Cultures of rat pulmonary macrophages release LTs in response to asbestos exposure. Macrophages release primarily LTB4 but some LTC4 is also liberated. We intend to characterize further the products released by asbestos from rat macrophages and to explore the possible relationship between macrophages and the development of asbestosis. We have also found that mouse skin is very rich in prostaglandin synthase and essentially devoid of lipoxygenase ativity. The major cyclo-oxygenase product is PGE2 as characterized by high pressure liquid chromatography and gas chromatography-mass spectrometry.